Risk of hyperkalemia in women taking ethinylestradiol/drospirenone and other oral contraceptives.
BACKGROUND
The oral contraceptive ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) contains a progestin component that possesses potassium-sparing diuretic activity similar to spironolactone. We sought to determine whether EE/DRSP use might lead to adverse effects possibly attributable to hyperkalemia.


METHODS
This was a matched cohort study in which we identified oral contraceptive (OC) initiators between July 2001 and June 2004 within a large, US health plan. We matched EE/DRSP initiators to other OC initiators in a 1:2 ratio on the basis of a prediction model (propensity score) of EE/DRSP initiation that incorporated dozens of characteristics. We identified insurance claims mentioning hyperkalemia, related clinical outcomes (electrolyte disturbances, arrhythmia, syncope, myocardial infarction) and verified the underlying condition through medical record review.


RESULTS
There were 22,429 EE/DRSP initiators matched to 44,858 other OC initiators, with an average follow-up of 7.6 months. A composite clinical surrogate hyperkalemia end point occurred with equal frequency in the compared groups [118 cases in EE/DRSP and 260 in comparators; rate ratio (RR) 0.9, 95% confidence interval (CI) 0.7-1.1]. The individual hyperkalemia surrogate end points exhibited similar results. One EE/DRSP initiator and four comparators were diagnosed specifically with hyperkalemia (RR 0.5, 95% CI 0.0-4.9). The results were not different when we accounted for changes in OC use during follow-up.


CONCLUSIONS
EE/DRSP initiators are no more likely than other OC initiators to experience hyperkalemia or related clinical outcomes which could be caused by hyperkalemia during follow-up.
Loughlin
Jeanne
J
Ingenix i3 Drug Safety, Waltham, MA 02451, USA. jeanne.loughlin@i3drugsafety.com
Seeger
John D
JD
Eng
P Mona
PM
Foegh
Marie
M
Clifford
C Robin
CR
Cutone
Jennifer
J
Walker
Alexander M
AM
D000328:Adult; D000736:Androstenes / Q000009:adverse effects*; D015331:Cohort Studies; D003267:Contraception; D003276:Contraceptives, Oral / Q000009:adverse effects*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects; D004997:Ethinyl Estradiol / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced* / Q000453:epidemiology; D016015:Logistic Models; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects; D017063:Outcome Assessment, Health Care; D012306:Risk; D014481:United States; D014486:United States Food and Drug Administration
D000736:Androstenes; D003276:Contraceptives, Oral; D003277:Contraceptives, Oral, Combined; D004967:Estrogens; D000451:Mineralocorticoid Receptor Antagonists; D004997:Ethinyl Estradiol; C035144:drospirenone